1. Field of the Invention
The present invention relates to an improved process for preparing isoflurane from PFE.
2. Description of Related Art
The compound isoflurane (1-chloro-2,2,2-trifluoroethyl difluoromethyl ether) has the structural formula: 
and is a well known anesthetic. The compound, and methods for its preparation are described in U.S. Pat. Nos. 3,535,388, and 3,535,425. Its pharmacological properties are described in Anesthesiology 35, 8-53 (1971); and in Can. Anaesth. Soc. J. 18, 376-407 (1971).
The conventional process for preparing isoflurane involves reaction of 2,2,2-trifluoroethyl difluoromethyl ether, (or xe2x80x9cpentafluoro etherxe2x80x9d which is also known as xe2x80x9cPFExe2x80x9d), and has the structural formula: 
with elemental chlorine under light. Thus, the chlorination reaction proceeds according to the following scheme: 
In the conventional process, the chlorine is introduced into a vessel containing substantially dry PFE illuminated with an ultraviolet light in a quartz housing. This process requires an expensive vessel made of corrosion-resistant alloy capable of withstanding HCl under pressure. In fact, during the chlorination reaction the pressure continues to increase because of the continuing production of HCl. To mitigate this problem it is necessary to remove HCl during the process without losing chlorine, PFE or the product. This requires a high pressure, corrosion-resistant alloy fractional distillation column with a low temperature condenser to provide the refluxing of liquid HCl necessary to separate the components of the mixture. Even with this elaborate distillation procedure there are losses of reactants with the removed HCl. Moreover, several impurities are generated, which are difficult to separate from the isoflurane product.
Accordingly, there is the need in the art for an improved process for preparing isoflurane, which removes the need for elaborate distillation procedures, corrosion-resistant pressure vessels, and elaborate drying procedures, and eliminates the losses encountered with the removed HCl, and reduces the amounts of impurities generated.
These and other objects were met by the present invention, which relates to an improved process for preparing isoflurane, which comprises reacting 2,2,2-trifluoroethyl difluoromethyl ether with chlorine in the presence of light, wherein the improvements comprise conducting the reaction in the presence of water, choosing the temperature to improve the yield, and using higher conversions to lower costs with little effect upon yield.